GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements
Author(s)
Type
Journal Article
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1,138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
Date Issued
2022-08-17
Date Acceptance
2022-04-08
Citation
Nature Communications, 2022, 13
ISSN
2041-1723
Publisher
Nature Research
Journal / Book Title
Nature Communications
Volume
13
Copyright Statement
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Sponsor
Foundation for the National Institutes of Health (FNIH)
The Academy of Medical Sciences
British Heart Foundation
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
RFP16
REF:SBF005\1050
RE/18/4/34215
RDB02
Subjects
Bile Acids and Salts
Cholestasis, Intrahepatic
Female
Genome-Wide Association Study
Humans
Infant, Newborn
Pregnancy
Pregnancy Complications
Premature Birth
NIHR BioResource
Genomics England Research Consortium Collaborators
Humans
Cholestasis, Intrahepatic
Pregnancy Complications
Premature Birth
Bile Acids and Salts
Pregnancy
Infant, Newborn
Female
Genome-Wide Association Study
Publication Status
Published
Article Number
ARTN 4840